Apoa2 humanized transgenic mouse – line delta

The mice are hemizygous for the human apolipoprotein A2 (ApoA2) gene expressed under the control of the homologous promoter (-911/+2045). They are humanized because they are deficient in mouse ApoAII following backcrosses with APOA2 Knockout mice (KO-ApoA2 described in ref. 1). KO-ApoA2 mice have been fully backcrossed into the C57BL/6 background before mating with human ApoAII transgenic mice. ApoAII is expressed only in liver. Its plasma concentration is 50 mg/dl with chow diet (1.5 to 2 times the physiological concentration in humans), and increases up to 70 mg/dl with a high fat diet.In the fed state, plasma HDL levels are decreased by 45% (compared to C57BL/6 mice) and triglycerides are increased up to 10-fold, due to decreased VLDL catabolism. In the fasted state, mice display a 34% reduction in HDL and normal triglyceridemia (2).

Interest / Relevance: ApoAII is the second most important protein of HDL (High Density Lipoproteins) after ApoAI, and ensures HDL structural stability.Human ApoAII promotes cholesterol efflux mediated by ABCA1 (3). Useful for studying the role of human apo AII moderately overexpressed, and the influence of dietary and hormonal treatments (due to the presence of the homologous promoter).

Keywords: ApoA2

Publications:

11- Dramatically decreased high density lipoprotein cholesterol increased remnant clearance and insulin hypersensitivity in apolipoprotein A-II knockout mice suggest a complex role for apolipoprotein A-II in atherosclerosis susceptibility. Weng W. and Breslow JL. Proc Natl Acad Sci U S A 1996 93:14788-94.2- Apolipoprotein A-II/A-I ratio is a key determinant in vivo of HDL concentration and formation of pre-beta HDL containing apolipoprotein A-II. Pastier D. et al. Biochemistry 2001 40:12243-53.3- Opposite effects of plasma from human apolipoprotein A-II transgenic mice on cholesterol efflux from J774 macrophages and Fu5AH hepatoma cells. Fournier N. et al. Arterioscler Thromb Vasc Biol 2002 22:638-43.

Reference:

RT00423